Acid-related gastrointestinal conditions such as non-ulcer dyspepsia, duodenal ulcer, gastric ulcer, stress gastritis, gastroesophageal reflux disease (GERD), pancreatic insufficiency, bile acid-mediated diarrhea, biliary reflux, and constipation are prevalent and require effective management. Antacids have been a cornerstone of treatment for many years, initially serving as first-line therapy against peptic ulcer disease. They provide symptomatic relief by directly neutralizing gastric acid, thereby elevating gastric pH, reducing pepsin activity, restoring acid-base balance, and promoting secretion of prostaglandins and bicarbonates. Antacids demonstrate therapeutic efficacy even at low doses, with minimal side effects, sustained elevation of gastric pH, rapid and prolonged pain relief, and effective reduction of gas symptoms. This review examines the indications, types with examples, mechanisms of action, pharmacodynamics, pharmacokinetics, adverse effects, drug interactions, contraindications, toxicity, and other crucial aspects of antacid therapy in clinical practice, focusing on essential considerations for managing patients with heartburn and mild GERD.